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Signaling through BMPR-IA regulates quiescence and long-term activity of neural stem cells in the adult hippocampus.
Cell Stem Cell 7, 78-89 (2010)
Neural stem cells (NSCs) in the adult hippocampus divide infrequently, and the molecules that modulate their quiescence are largely unknown. Here, we show that bone morphogenetic protein (BMP) signaling is active in hippocampal NSCs, downstream of BMPR-IA. BMPs reversibly diminish proliferation of cultured NSCs while maintaining their undifferentiated state. In vivo, acute blockade of BMP signaling in the hippocampus by intracerebral infusion of Noggin first recruits quiescent NSCs into the cycle and increases neurogenesis; subsequently, it leads to decreased stem cell division and depletion of precursors and newborn neurons. Consistently, selective ablation of Bmpr1a in hippocampal NSCs, or inactivation of BMP canonical signaling in conditional Smad4 knockout mice, transiently enhances proliferation but later leads to a reduced number of precursors, thereby limiting neuronal birth. BMPs are therefore required to balance NSC quiescence/proliferation and to prevent loss of the stem cell activity that supports continuous neurogenesis in the mature hippocampus.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Central-nervous-system; Bone morphogenetic protein; Dentate gyrus; Progenitor cells; Neurogenesis; Expression; Receptor; Noggin; Brain; Differentiation
ISSN (print) / ISBN
1934-5909
e-ISSN
1875-9777
Zeitschrift
Cell Stem Cell
Quellenangaben
Band: 7,
Heft: 1,
Seiten: 78-89
Verlag
Cell Press
Verlagsort
Cambridge, Mass.
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed